Chronic nerve compression syndrome is a common clinical problem that has assumed epidemic proportions in the 1990s. Although an association between mechanical pressure on the median nerve and carpal tunnel syndrome (CTS) has been hypothesized, neither the relationship between the severity and duration of such pressure and the resultant CTS, nor the underlying pathophysiology have been elucidated. To understand how mechanical pressure in the wrist leads to alterations in median nerve function and nerve morphology, we have developed an in vivo rabbit model in which graded. reversible compressive forces can be applied in the carpal canal and neurophysiologic and biologic consequences monitored. Static compressive loading will be applied to the rabbit median nerve with pneumatic balloon catheters fixed at the transverse carpal ligament to create CTS. The duration of exposure required to cause carpal tunnel syndrome as a function of the applied pressure will be determined. The endpoint of CTS will be defined as an increase in motor latency that is consistently observed over a two-week time period by nerve conduction studies/electromyography (NCS/EMG). Changes in nerve vascularity and microcirculation will be studied by in vivo microscopic analysis prior to sacrifice. Histologic specimens will be prepared and graded for nerve morphology and inflammatory response. This information will be used to develop an understanding of the chronology of events that occurs with CTS. Our goal is to establish a dose-response relationship between pressure within the carpal canal and CTS. We hypothesize that in the pathomechanics of CTS, there is a significant relationship between pressure, duration of exposure to pressure, and various inflammatory and vascular events that surround CTS. These data will have significant implications for human CTS. In the future, this model may serve to test the modulation of threshold pressure for developing CTS by various treatments in an effort to prevent CTS. Ultimately, we wish to realize a comprehensive understanding of pathophysiology of CTS, its prevention, and when it occurs, its treatment. We will simulate clinical CTS reversal, as in carpal tunnel release, by deflating balloon catheters in animals in which CTS has already been induced. From this animal model of CTS reversal, we will generate a pathophysiology that relates duration and amount of pressure to resultant CTS reversal with NCS/EMG, microscopic evaluation of nerve vascularity, and tissue analysis.